Membrane proteins perform many important biological functions, are targets of key clinical drugs, and make up nearly a third of the human proteome. Despite their prominence and importance, membrane proteins still account for only a small fraction of known protein structures. The reasons for this discrepancy are numerous, but can be summarized by stating that membrane proteins present many difficulties, including expression, purification, and crystallization. At the core of these difficulties lies the interaction between protein and lipid, the defining characteristic of a membrane protein. The isolation of membrane proteins usually requires that they be removed from the membrane by detergent solubilization, a process that often disrupts the native protein-lipid interaction and can lead to non-native protein conformations. Better tools to handle membrane proteins are needed.